Tesaro Initiates Rolling Submission for Niraparib in Ovarian Cancer

The FDA has granted a fast track designation to niraparib, allowing the initiation of a rolling submission of data for potential approval for the PARP inhibitor as a treatment for women with recurrent platinum-sensitive ovarian, fallopian tube, or primary peritoneal cancer.

Mary Lynne Hedley, PhD

The FDA has granted a fast track designation to niraparib as a treatment for women with recurrent platinum-sensitive ovarian, fallopian tube, or primary peritoneal cancer, according to the company developing the PARP inhibitor, Tesaro. Under this designation, the company has initiated a rolling submission of data from the phase III NOVA for a new drug application (NDA). Full submission of the NDA to the FDA is anticipated before the end of 2016.

In the phase III trial, niraparib improved median progression-free survival (PFS) by 15.5 months versus placebo for patients responding to platinum-based chemotherapy who harbored a germline (gBRCA) mutation, according to results released by the company. In those with non­—gBRCA-mutated tumors with homologous recombination deficiency (HRD)-positivity, there was a 9.1-month PFS advantage seen with niraparib versus placebo.

“The initiation of this rolling NDA submission is a significant milestone for Tesaro, and we are committed to working collaboratively with the FDA to advance the review of the niraparib application,” Mary Lynne Hedley, PhD, president and COO of Tesaro, said in a statement. “We look forward to presentation of data from the phase III NOVA trial of niraparib in a Presidential Symposium session at the European Society for Medical Oncology congress on October 8.”

The phase III NOVA study enrolled more than 500 patients across 2 independent cohorts that randomized patients in a 2:1 ratio to receive niraparib at 300 mg daily or placebo. The first cohort enrolled patients with gBRCA mutations and the second enrolled individuals who were not gBRCA-positive but were either HRD-positive or HRD-negative. The HRD-positive group could include those with somatic BRCA alterations. HRD testing was conducted using Myriad’s myChoice HRD test.

Patients in the trial had histologically confirmed ovarian, fallopian tube, or primary peritoneal cancer that was high-grade serous histology or had a known gBRCA mutation. All patients had received ≥2 prior courses of platinum-based therapy and were considered platinum sensitive. The primary endpoint of the study was PFS, with secondary outcome measures focused on overall survival and safety.

The median PFS in gBRCA mutation carriers was 21.0 months with niraparib versus 5.5 months with placebo, representing a 73% improvement in the risk of progression or death (HR, 0.27; P <.0001). For those with HRD-positive tumors, the median PFS was 12.9 months with niraparib versus 3.8 months with placebo (HR, 0.38; P <.0001).

Niraparib continued to show a benefit over placebo for patients with ovarian cancer regardless of HRD or gBRCA status. In the cohort of patients with non-gBRCA mutations who were either HRD-positive or HRD-negative, the median PFS was 9.3 months with niraparib versus 3.9 months with placebo, representing a 55% improvement with the PARP inhibitor (HR, 0.45; P <.0001).

The most frequently observed grade 3/4 treatment-emergent adverse events (AEs) with niraparib were thrombocytopenia (28.3%), anemia (24.8%), and neutropenia (11.2%). Overall, 14.7% of patients discontinued treatment with niraparib during the trial compared with 2.2% of those in the control arm. The rates of secondary MDS or AML were similar between the niraparib and placebo arms (1.3% vs 1.2%, respectively).

"Importantly, these results show activity of niraparib in a population of ovarian cancer patients beyond those with germline BRCA mutations. In keeping with our mission of responsible drug development, NOVA was designed to define those patients most likely to benefit from niraparib treatment and, in so doing, optimize the benefit/risk profile for patients," Hedley, said in a statement, when the results were announced in late June.

Niraparib continues to be developed in various settings for patients with cancer. The single-arm phase II QUADRA trial is exploring niraparib in patients with high-grade serous ovarian cancer who were previously treated with ≥3 prior lines of chemotherapy. The phase III PRIMA study is looking at the PARP inhibitor as a frontline therapy for women with ovarian cancer. In breast cancer, the phase III BRAVO study is comparing the medication with physician's choice for those with gBRCA-mutant breast cancer.

Tesaro also plans to submit data from the NOVA study to the European Medicines Agency for approval consideration in the European Union. Full data from the NOVA study have not yet been presented.

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